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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not reported, research proposal dated 1983-02-13; tables dated 1984-01-31
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP study, but the test parameters documented are sufficient to accept the data (Klimisch et al., 1997).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Objective of study:
excretion
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Principles of method if other than guideline:
Three animals were used. No sufficient information about test substance, experimental animals, their housing and feeding conditions. One dose level of test substance was administered. No interpretation of results.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 14C Labeled Diallyl-Diglycol Carbonate
- Substance type: data not available
- Physical state: data not available
- Analytical purity: data not available
- Impurities (identity and concentrations): data not available
- Composition of test material, percentage of components: data not available
- Isomers composition: data not available
- Purity test date: data not available
- Lot/batch No.: 1222-145, assay number 81-221797
- Expiration date of the lot/batch: data not available
- Radiochemical purity (if radiolabelling): Scintillation counting determinations showed that a 100 microliter dose contained 0.97 microcuries of 14C labeled CR-39.
- Specific activity (if radiolabelling): data not available
- Locations of the label (if radiolabelling): (allyl-14C1) moiety of diallyl-diglycol
- Expiration date of radiochemical substance (if radiolabelling): data not available
- Stability under test conditions: data not available
- Storage condition of test material: data not available
- Other:
The 14C labeled CR-39 utilized in this study was synthesized by New England Nuclear and was provided by the sponsor. A precipitant formed when the material was dissolved in absolute EtOH (ethanol). The EtOH soluble fraction was assayed by thin layer chromatography using Silica Gel G. and a hexane:ether (40:60, v/v) solvent system. The EtOH soluble fraction had the same rf value as a CR-39 reference standard. Only the EtOH soluble fraction was used in these studies.
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: data not available
- Age at study initiation: adult animals
- Weight at study initiation: data not available
- Fasting period before study: data not available
- Housing: individually
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): data not available
- Water (e.g. ad libitum): data not available
- Acclimation period:data not available

ENVIRONMENTAL CONDITIONS
data not available

Administration / exposure

Route of administration:
intramuscular
Vehicle:
ethanol
Details on exposure:
TYPE OF EXPOSURE: intramuscular

Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
100 µL
No. of animals per sex per dose:
3
Control animals:
no
Positive control:
no
Details on study design:
- Dose selection rationale: not reported
- Rationale for animal assignment (if not random): not applicable
Details on dosing and sampling:
PHARMACOKINETIC STUDY ( excretion)
- Body fluids sampled (delete / add / specify): urine, faeces and respirated carbon dioxide
- Time and frequency of sampling: daily for 7 days
- Method type(s) for identification: (Liquid scintillation counting)


METABOLITE CHARACTERISATION STUDIES
- Tissues sampled: liver, kidney, thigh (site of injection)
- Time and frequency of sampling: at termination
- From how many animals: (samples pooled) 3
- Method type(s) for identification: wet ashing method of Bucks and Maibach
- Limits of detection and quantification: data not available
Statistics:
not reported

Results and discussion

Preliminary studies:
The present study is conducted according to a research proposal; no further data available.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
not applicable
Details on distribution in tissues:
see table 2 in "Remarks on results including tables and figures"
Transfer into organs
Transfer type:
other: not applicable (excretion study)
Observation:
other: not applicable (excretion study)
Details on excretion:
see table 2 in "Remarks on results including tables and figures"
Toxicokinetic parameters
Toxicokinetic parameters:
other: not measured

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
not applicable

Any other information on results incl. tables

Table 1: Recovery % of test substance

 

Animal 1

Animal 2

Animal 3

Urine*

20.41

18.75

20.57

Feces

9.15

6.82

3.67

CO2**

70.77

70.77

70.77

Kidneys

0.08

0.16

0.16

Livers

1.62

0.21

4.46

Carcass

6.44

3.24

4.61

Thigh***

2.89

6.14

7.43

Summe

111.36

106.09

111.67

* percent of applied 14C dose

** carbon dioxide was a pooled animal collection

*** site of IM (intramuscular) injection

The total percent recovery of the compound was 109.7 (standard deviation of 3.1). The excess above 100% is due to extremely low counts above background, large volumes of the tissue homogenate preparations and the small aliquot utilized in the wet ashing procedure.

The 14C label on the CR-39 was predominately excreted via respiration (70 .77% of the injected dose). Over 60% of the dose was collected in the respired carbon dioxide within the first 24 hours from application.

Elimination of the 14C label on the CR-39 into the urine accounts for 19.9% (standard deviation of 1.0) of the dose with 19% of the dose being eliminated within the first 24 hours from application.

Two graphs are enclosed (see "Attached background material"): The first is a linear plot of the average % dose excreted into the urine per hour versus time at the midpoint of the collection period. The second is a semilog plot of the % dose excreted into the urine per hour versus time at the midpoint of the collection period.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results only one dose level was tested
Based on the study results, there was no retention of the test substance in organs examined. The test substance was predominantly excreted via respiration.
Executive summary:

This study was performed to determine the excretion parameters of the allyl-14C1- label on diallyl-diglycol carbonate (CR-39) into the urine, feces, and respired carbon dioxide as well as deposition into the liver, kidney, thigh (site of injection), and remaining carcass following a single parenteral dose utilizing the guinea pig experimental animal model.

The percent recovery of the test substance in parameters examined was 100% seven days after the administration.